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Background: Patients with preclinical left ventricular (LV) diastolic dysfunction (DD) are prone to develop heart failure with preserved ejection fraction. Although left atrial (LA) enlargement and deterioration of LA function in apparent DD and heart failure with preserved ejection fraction have been previously described, data regarding phasic LA strain (LAS) in preclinical DD are scarce., Methods: In a cross-sectional trial, echocardiographic parameters of DD, LA volume index, and global LA reservoir, conduit, and pump function were prospectively analyzed in 473 women from the general population in Berlin, Germany (BErlin Female RIsk evaluation (BEFRI) study), using standard and two-dimensional speckle-tracking echocardiography., Results: One hundred thirty-one women (29.7%) showed early-stage DD (impaired relaxation [DD1]) and 22 (5.0%) showed an echocardiographically more advanced stage of DD (pseudonormal filling [DD2]). Compared with women with normal diastolic function (DD0), those with DD1 displayed lower LA reservoir and conduit function (DD0, 43.2 ± 8.5% and 27.2 ± 8.0%; DD1, 33.3 ± 8.0% and 16.1 ± 7.1%; P < .001) but significantly higher LA pump function (DD0, 17.6 ± 5.4%; DD1, 18.9 ± 5.5%; P < .05). In patients with DD2, all three phases of LAS were markedly impaired compared with those with DD0 (reservoir, conduit, and pump function, 29.0 ± 6.3%, 15.1 ± 5.4% [P < .001], and 14.9 ± 4.1% [P < .05], respectively). LA reservoir and conduit function was significantly associated with DD; in receiver operating characteristic curve analysis, these parameters showed higher diagnostic accuracy in detecting early DD compared with LA volume index. In multivariate analysis, LA reservoir strain remained significantly associated with DD., Conclusions: All three components of LAS showed specific alterations in different stages of DD. LA reservoir and conduit function was markedly reduced before symptoms, LA enlargement, and elevations of noninvasively estimated LV filling pressures occurred. Analysis of LA function featured higher discriminative strength in diagnosing early-stage DD compared with the well-established parameter LA volume index. Assessment of LAS allows diagnosis of impaired LA function and DD in a subclinical stage and might enable timely preventive and therapeutic interventions., (Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease is the most common cause of death in men and women worldwide. Men develop most, but not all, cardiovascular diseases at an earlier age while the number of affected women significantly increases with higher age. Heart failure (HF) is a common cause of cardiovascular death and carries a poor prognosis in both genders. Risk factors and myocardial adaptations in HF in men and women are different. Female hearts develop a more favorable physiological form of myocardial remodeling than male hearts. This may be related to sex hormones, estrogens and testosterone. A clinical study for gender differences in human aortic stenosis supports the hypotheses. HF management differs between both sexes, with underdiagnosis and undertreatment and less use of invasive therapies in women. Nevertheless, women frequently have better outcomes than men. Gender research will contribute directly to patient-oriented benefit by suggesting clinical protocols.

Heart failure (HF) is a leading cause of cardiovascular mortality and morbidity in the Western world. It affects men at younger age than women. Women have more frequently diastolic HF, associated with the major risk factors of diabetes and hypertension and men have more frequently systolic HF because of coronary artery disease. Under stress, male hearts develop more easily pathological hypertrophy with dilatation and poor systolic function than female hearts. Women with aortic stenosis have more concentric hypertrophy with better systolic function, less upregulation of extracellular matrix genes and better reversibility after unloading. Stressed female hearts maintain energy metabolism better than male hearts and are better protected against calcium overload. Estrogens and androgens and their receptors are present in the myocardium and lead to coordinated regulation of functionally relevant pathways. Atrial fibrillation (AF) is a more ominous sign in women than in men. Men with end-stage cardiomyopathy more frequently have auto-antibodies than women. Women receive less guideline-based diagnostics and therapy. Expensive and invasive therapies such as advanced pacemakers and transplantation are underused in women. Drug studies point at sex differences in efficacy. Despite worse diagnostics and therapy, prognosis is better in women than in men.

Background: Cardiac angiotensin converting enzyme (ACE) is activated by an increase in wall stress and is involved in remodeling processes. Heart failure is often treated with ACE inhibitors and diuretics although diuretic treatment could activate the renin-angiotensin system (RAS)., Aims: To examine the effects of diuretic treatment on cardiac and circulating RAS in post-infarction chronic heart failure., Methods: Myocardial infarction was produced by coronary artery ligation in spontaneously hypertensive rats. The rats were randomly assigned to receive either ramipril (1 mg/kg/day), furosemide (4 mg/kg/day), or combination therapy for 6 weeks, commencing 2 weeks after infarction., Results: All three treatment protocols equivalently attenuated reactive hypertrophy of the right ventricle and ventricular septum and improved left ventricular systolic function. Both cardiac ACE mRNA and activity were significantly increased in untreated rats. This increase was attenuated by both ramipril and furosemide and further depressed by the combination. The increase in activity was completely inhibited by either agent alone. Plasma renin activity was upregulated by ramipril or ramipril plus furosemide but not influenced by infarction or furosemide alone., Conclusions: Furosemide and ramipril significantly reduced cardiac ACE and remodeling. Diuretics work favorably and do not interfere with the effects of ACE inhibitors. Possibly, a reduction in wall stress due to decreased volume overload accounts for the effects of diuretics on cardiac ACE in the treatment of post-infarction remodeling in hypertensive hearts. These data suggest a new mechanism for the frequently observed beneficial effect of diuretics in heart failure.

Extracellular matrix (ECM) remodeling and increased matrix metalloproteinase (MMP) expression and activity have been observed to be relevant in the development of heart failure (HF). We examined the effects of ramipril alone or with furosemide on ECM in a heart failure model. HF was induced by occlusion of the left coronary artery in spontaneously hypertensive rats (SHR). Rats were assigned to placebo (n=9), ramipril 1 mg/kg/day (n=11), furosemide 2 x 2 mg/kg/day (n=7) or both (1 mg/kg/day + 2 x 2 mg/kg/day n=8). LV-function, collagen content, MMP/TIMP (tissue inhibitor of matrix metalloproteinases) protein- and mRNA-expression were examined in non-infarcted LV tissue. MMP-2/TIMP-4 ratio was increased in HF. Ramipril reduced MMP-2 expression (active form), collagen type I mRNA expression and content and increased TIMP-4 levels associated with decreased left ventricular end diastolic pressure (LVEDP), mortality rate and increased LV pressure (LVP). Combination therapy with furosemide is less efficient with regard to collagen content and MMP-2 (active form) reduction but did not worsen beneficial effects of ramipril on LV function and mortality rate. Furosemide alone had no effect on MMP-2 (active form) expression, collagen content, LV function and mortality rate. Prevention of LV dilatation by ramipril was associated with decreased gelatinolytic activity and increased MMP-inhibition in heart failure SHR. Furthermore, ramipril reduced fibrosis by enhanced interstitial collagenase expression. Furosemide did not show the beneficial effects of ramipril on ECM remodeling but did not worsen LV function. Positive effects of furosemide treatment alone on LV remodeling and function were not observed., (Copyright 2002 Academic Press.)